Abstract:

<bold>Background</bold>: The safety of bevacizumab in older metastatic colorectal cancer (mCRC) patients is not well understood. The purpose of this analysis was to determine the prevalence of treatment–associated adverse events (AEs), to describe patterns of bevacizumab use in patients with preexisting comorbidities, and to determine incidence of and risk factors for serious adverse events in patients who do and do not receive bevacizumab. <bold>Methods</bold>: Patients age ≥65 were identified from SEER–Medicare and categorized by mCRC diagnosis pre and post–bevacizumab approval (2001–3 vs. 2005–7). Preexisting conditions known to increase risk of bevacizumab– related AEs were identified in the year pre– diagnosis. Factors associated with bevacizumab receipt were identified using logistic regression. Incidence rates for all AEs and specific serious AEs (deep vein thrombosis (DVT), pulmonary embolus (PE), stroke, myocardial infarction (MI), gastrointestinal (GI) hemorrhage and perforation) were determined. A competing risks regression analysis was used to determine risk factors for first AE. <bold>Results</bold>: Of 6,821 total patients, 3,282 (48%) were diagnosed after 2005 and 622 (9%) received first-line bevacizumab. Likelihood of bevacizumab receipt was lower in patients age ≥ 75 (OR 0.41, 95% CI 0.36–0.47), non–whites (OR 0.67, 95% CI 0.55–0.81), patients with higher comorbidity index (OR 0.52, 95% CI 0.44–0.62), and patients with preexisting cerebrovascular disease (0.49, 95% CI 0.33–0.72). Preexising gastrointestinal conditions, by contrast, were associated with an increased likelihood of bevacizumab receipt (OR 2.26, 95% CI 1.96–2.61). Overall AE incidence rate was not increased among patients receiving first–line bevacizumab compared to patients receiving first–line chemotherapy alone (141 AEs vs. 135 AEs / 100,000 person–days (PD)). Incidence rates for specific AEs (DVT/PE, stroke, MI, GI hemorrhage, and perforation) were also similar between patients who did and did not receive first–line bevacizumab. In a competing risks regression, bevacizumab receipt (2005–7) was not associated with an increased risk of first AE compared with receipt of chemotherapy alone (2001–7) when controlling for age, race, comorbidity index, gender, chemotherapy regimen, and preexisting conditions (HR 0.97, 95% CI 0.87–1.08, p=0.55). <bold>Conclusions</bold>: In a population of older mCRC patients, bevacizumab receipt was less likely in patients who were older, non–white, and had preexisting cerebrovascular comorbidities. First–line bevacizumab receipt was not associated with increased overall AE incidence or risk of first AE compared with chemotherapy alone.